In addition to the need for rapid and accurate analyte detection is a current need for the sensor technology to perform “out of the box” or otherwise require little or no pre-use testing and or validating. Attempts to provide electrochemical sensors with little or no pre-use testing have been addressed in a number of ways, for example by using software or algorithm-based validation protocols or by incorporating an aqueous reservoir or environment with a known analyte concentration about the sensor. In certain cases, such as an intensive care units (ICUs) setting or for continuous glucose monitoring (CGM) applications, it would be desirable to avoid or eliminate the need to validate or otherwise test the sensor just prior to use. Thus, the current amperometric sensors available on the market may not be capable of “out of the box” performance needed for specific applications, such as ICU monitoring of analyte levels in a subject.
In certain medical applications, patients in ICU or other emergency situations may be often fitted with invasive appliances such as catheters so that vital fluids or medicine may be administered intravenously. A physician determining a fluid dosage to be provided to a patient intravenously may need to know symptoms as quickly as possible that may only be determined through blood tests. Just how quickly the information is needed depends on the gravity of the situation. In some cases, the speed with which a physiological parameter may be determined may be the difference between life and death. In those situations, the requirement of having to pre-test or otherwise validate the sensor just prior to use, just as the practice of drawing a blood sample and sending it off for laboratory analysis, may be entirely unacceptable and/or detrimental to a patient.
A more timely method for measuring blood chemistry to ascertain a physiological parameter of interest may eventually be perfected. Thus, there exists an unmet need to provide intravenous amperometric sensing, in which the concentration of an analyte present in a patient's bloodstream may be determined by locating, within the circulatory system, sensor comprising an electrochemical analyte sensor that has been pre-tested and/or validated in-vitro and produces a rapid and accurate electrical current proportional to the true analyte concentration.
Moreover, pre-testing of electrochemical devices may result in performance that is not commensurate with actual end-use, and as a result, potentially viable sensor constructs may be erroneously dismissed. It is generally known that when testing an electrochemical analyte sensor in vitro, the testing solution is buffered to simulate the pH of the actual end-use environment of the sensor. Typically the buffer solution is PBS and the pH is adjusted to that of physiological fluids found in the test subject (e.g., blood, interstitial fluids, urine, etc.). It is also generally observed in sensor development and/or quality assurance (QC) testing of electrochemical analyte sensors that the output signal may drift over a period of time at a given (and relatively constant) analyte concentration range. When such a drift is observed, it is typically regarded as an indication that the sensor construct and any of its components is not optimized and/or otherwise inadequate and may result in re-design or QC rejection of the sensor and possibly all of the sensors fabricated together therewith.
Thus, a testing method for electrochemical analyte sensors that otherwise provides performance that is commensurate with actual end-use and/or adequately buffers the microenvironment of an enzyme within a multi-layer analyte sensing membrane, is desirable.